The severity of NAFLD is associated with gut dysbiosis and shift in the metabolic function of the gut microbiota
By J. Boursier, Olaf Mueller, M. Barret, M. Machado, L. Fizanne, Félix Araújo-Pérez, C. Guy, P. Seed, J. Rawls, Lawrence A. David and 4 more. Hepatology, 2016
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Several animal studies have emphasized the role of gut microbiota in nonalcoholic fatty liver disease (NAFLD). However, data about gut dysbiosis in human NAFLD remain scarce in the literature, especially studies including the whole spectrum of NAFLD lesions. We aimed to evaluate the association between gut dysbiosis and severe NAFLD lesions, that is, nonalcoholic steatohepatitis (NASH) and fibrosis, in a well‐characterized population of adult NAFLD. Fifty‐seven patients with biopsy‐proven NAFLD were enrolled. Taxonomic composition of gut microbiota was determined using 16S ribosomal RNA gene sequencing of stool samples. Thirty patients had F0/F1 fibrosis stage at liver biopsy (10 with NASH), and 27 patients had significant F≥2 fibrosis (25 with NASH). Bacteroides abundance was significantly increased in NASH and F≥2 patients, whereas Prevotella abundance was decreased. Ruminococcus abundance was significantly higher in F≥2 patients. By multivariate analysis, Bacteroides abundance was independently associated with NASH and Ruminococcus with F≥2 fibrosis. Stratification according to the abundance of these two bacteria generated three patient subgroups with increasing severity of NAFLD lesions. Based on imputed metagenomic profiles, Kyoto Encyclopedia of Genes and Genomes pathways significantly related to NASH and fibrosis F≥2 were mostly related to carbohydrate, lipid, and amino acid metabolism. Conclusion: NAFLD severity associates with gut dysbiosis and a shift in metabolic function of the gut microbiota. We identified Bacteroides as independently associated with NASH and Ruminococcus with significant fibrosis. Thus, gut microbiota analysis adds information to classical predictors of NAFLD severity and suggests novel metabolic targets for pre‐/probiotics therapies. (Hepatology 2016;63:764–775)
Subfields: Epidemiology, Infectious Diseases, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/0be5c71b4fd4ad3e223a9fe443855198d0c53c92
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Citations in the corpus
- Gut microbiome based metagenomic signature for non-invasive detection of advanced fibrosis in human nonalcoholic fatty liver disease (2017, neutral): “(Boursier et al., 2016) They imputed metagenomic functions from the 16S sequence data.”
- Liver inflammation and fibrosis. (2017, background): “Boursier and colleagues evaluated gut dysbiosis in NAFLD patients and found that Bacteroides abundance was independently associated with NASH and Ruminococcus with fibrosis (36).”
- Dietary lipids, gut microbiota and lipid metabolism (2019, background): “To date, no clinical study targeting the gut microbiota to specifically modify FXR signaling in NAFLD or NASH has been performed.”
- Role of Oxidative Stress in Pathophysiology of Nonalcoholic Fatty Liver Disease (2018, background): “) is associated with worse presentations of NASH [117].”
- Lipotoxicity and the gut-liver axis in NASH pathogenesis. (2018, background): “associated the presence of fibrosis stage F≥2 with changes in carbohydrate, lipid, and amino acid metabolism [108].”
- Non-alcoholic fatty liver disease and its relationship with cardiovascular disease and other extrahepatic diseases (2017, background): “178 Overall, many studies from the past years clearly highlighted a role for the gut microbiota in obesity-related disorders supporting the assumption that NASH might be associated with a ‘ microbiome signature ’ which could contribute to initiation of in fl ammation.”